Malignant Potential of Endometrial Polyps : A retrospective study

To estimate the potential risk of malignancy in endometrial polyps and to investigate the possible clinical risk factors. Clinical, sonographic, hysteroscopic and pathological data were reviewed of 337 women with pathologically confirmed endometrial polyps diagnosed in Qatar between 2000 and 2010. The polyps were benign in 95.6% of cases, pre-malignant in 2.3%, and malignant in 2.1 % of cases. Advanced age, menopausal status and vaginal bleeding were strongly associated with atypical hyperplasia and cancer. There appeared to be no association between the risk of malignancy and other clinical risk factors. Conclusions: There is a small risk of malignancy in endometrial polyps, mainly in post-menopausal patients of advanced age with symptomatic vaginal bleeding. In these circumstances, endometrial polyps should be managed aggressively as potential cancer and removal for histology is mandatory.


Introduction:
Endometrial polyps are benign, localized overgrowths of endometrial glands and stroma that surround a vascular core.Polyps may be pedunculated or sessile, single or multiple, and range in size from a few millimeters to many centimeters.They are common and are estimated to affect up to 20% of post-menopausal women. (1,2)ith the increased use of ultrasound, hysterosonography and hysteroscopy in the evaluation of women with abnormal uterine bleeding or post-menopausal bleeding, the diagnosis of endometrial polyps has become more frequent in the last few years.The prevalence rate of endometrial polyps ranges from 10% to 4 0 % a 4 ) in Address for correspondence: Abdel Baset F. Mohammed, MD Obstetrics and Gynecology Department, Women's Hospital Hamad Medical Corporation, P.O.Box 3050, Doha, Qatar E-mail: abdull 63@yahoo.comwomen with abnormal uterine bleeding, and polyps are found in up to 12% of asymptomatic women in routine examinations. (2,5)hile endometrial polyps are often asymptomatic and detected incidentally, polyps are also a common cause of vaginal bleeding in both pre-menopausal and post-menopausal women. (1,2)In addition to symptoms, endometrial polyps have been associated with endometrial cancer.The risk of endometrial cancer in women with endometrial polyps has been reported to range from 0% to 4.8%. (1' 11 ' 15 ' 16) Hysteroscopy is considered the gold standard in the resection of endometrial polyps and evaluation of the endometrial cavity, allowing complete removal of the lesion and biopsy of suspicious areas in the adjacent endometrium. 0^ Despite the low prevalence rate of malignancy, various women have undergone surgical procedures for the removal of polyps without a precise indication.Thus, it is imperative to determine which women are at greater risk so that a more judicious surgical indication for hysteroscopic resection of endometrial polyps can be made. (3)The aim of this study was to estimate the potential risk of malignancy in endometrial polyps and to investigate the possible clinical risk factors associated with increased risk of malignancy.

Patients and Methods:
This retrospective study was conducted in the Department of Obstetrics and Gynecology, Women's Hospital, Hamad Medical Corporation, Doha, Qatar, after being accepted by the local research committee.All cases with endometrial polyps diagnosed at hysteroscopy or hysterectomy and confirmed by histopathology during the period from January 2000 to June 2010 were included in the study.Patients with known endometrial cancer previously diagnosed by curettage or pipelle biopsy, but found to have endometrial polyps, were excluded from the study.Medical records were reviewed for clinical, sonographic, hysteroscopic and pathological findings.The clinical variables assessed were; age, parity, menopausal status, presence of vaginal bleeding, obesity, hypertension, diabetes mellitus and use of hormonal therapy or tamoxifen.Women were considered post-menopausal if they had been amenorrheic for at least 1 2 months.Obesity was defined as body mass index (BMI) > 30 kg/ m2.Sonographic findings were reviewed for the size of the polyp and endometrial thickness.Diagnosis of endometrial polyp by ultrasound was made following a finding of focal endometrial thickening, associated with the presence of a vascular pediculum.Hysteroscopic findings were reviewed for the macroscopic aspect of the polyp and condition of the endometrium.Diagnostic hysteroscopy was performed using a 2.8 mm optical system (Karl Storz, Tuttlingen, Germany).Saline infusion was used for distension of the uterine cavity.Operative hysteroscopy was performed using a 10 mm resectoscope (Karl Storz).Distension of the uterine cavity was obtained with a 1.5% glycine solution.Resection of endometrial polyps was performed by electro-cautery using monopolar energy or by simple curettage under general anesthesia.Pathological findings were also reviewed.The presence of at least one endometrial polyp in the histological report was used as an inclusion criterion for the study.The most significant pathologic diagnosis was recorded for each subject.Endometrial and polyp pathologies were defined as; benign, simple hyperplasia, complex hyperplasia, simple or complex hyperplasia with atypia, or cancer, using standard pathologic criteria.Endometrial hyperplasia and cancer were characterized as arising in the polyp or the adjacent endometrium.
Statistical analysis was performed using chi-square test where appropriate; p < 0.05 was considered statistically significant.Incidences of benign, pre-malignant and malignant polyps were calculated.Possible clinical risk factors were investigated in relation to their association with atypical endometrial hyperplasia and cancer.All analyses were performed with SAS version 9.2 (SAS Institute Inc, Cary, NC).

Results:
Three hundred and thirty-seven women with an endometrial polyp pathologically confirmed as benign, pre-malignant or malignant were included in the study.The average age was 51 years (range 25-87 years); 39.8% were less than 50 years of age at the time of diagnosis and 52% of patients were post-menopausal The clinical and demographic characteristics of patients are reported in Table 1.
The sizes of the endometrial polyps ranged from 0.3 x 0.4cm to 5.8 x 7.2cm.The polyps were single (62%) or multiple (38%).In post-menopausal women the endometrial thickness was greater than 5mm in 88% of the cases while in pre-menopausal women the endometrial thickness was greater than 8mm in 85% of the cases.These women received a diagnosis of endometrial thickening.In seven patients, polyps were protruding through the cervix and were diagnosed clinically.One of these polyps was diagnosed as undifferentiated endometrial stromal sarcoma with polypoidal growth.The final pathological diagnoses showed 322 benign endometrial polyps (95.5%), eight (2.4%) pre-malignant polyps and seven (2.1 % ) malignant polyps (Table 2).Of the seven patients with endometrial carcinoma, three cancers were confined to the polyp.One patient with complex atypical hyperplasia had the disease confined to the polyp.
A univariable analysis of clinical risk factors associated with malignancy in endometrial polyps showed that advanced age (>50 years), menopausal status and presence of vaginal bleeding were significantly associated with atypical hyperplasia or endometrial cancer (Table 3).There was no association between risk of malignancy in endometrial polyps and other clinical risk factors.At diagnosis the cancer was confined to the endometrial polyp in 24%, while the adjacent endometrium was affected in 76%. Discussion: Endometrial polyps are defined as overgrowths of localized endometrial tissue. (18)They are encountered commonly in routine surgical pathology practice but opinions differ on whether they are intrinsically a marker for concurrent or subsequent malignancy. (19)Previous studies have demonstrated a significant increase in the incidence of pre-malignant and malignant polyps in post-menopausal women older than 60 years who have associated vaginal bleeding. (8,20)Some studies have also observed an association with other risk factors for malignancy such as obesity, use of tamoxifen, arterial hypertension and diabetes mellitus. (15) this study most (95.5%)pathologically confirmed endometrial polyps were benign and the overall risk of malignancy was 4.5%.These findings agree with those of prior studies, which reported a risk of cancer of up to 4.8% in women with endometrial polyps. (1,6' 7 ' 9_14) In addition to cancer, endometrial hyperplasia with atypia is frequently reported in this study (2.4%).' 6_8) .However, meta-analysis reported that the prevalence of pre-malignant or malignant polyps was 5.4% in postmenopausal women, 1.7% in reproductive-aged women, 4.15% in women with bleeding and 2.16% in asymptom-  atic women. (21)A second meta-analysis reported that the prevalence rate of pre-malignancy and malignancy was 3.57%. (10)These differences in prevalence rates may be attributed to different study designs, sample sizes, population differences, inclusion and exclusion criteria, and different methods used for the diagnosis of polyps, such as transvaginal ultrasound, hysterosonography, and hysteroscopy. (3,15)n this study, advanced age, symptomatic vaginal bleeding and menopausal status appeared to be the strongest risk factor for detection of atypical hyperplasia or cancer in a polyp.A number of previous studies have attempted to define risk factors for polyp-associated cancer.While data has been inconsistent, age, menopausal status and the presence of symptomatic vaginal bleeding are the factors most often cited. (1' 6 ~8' 22_25) Ferrazzi and colleagues (6) noted that the risk of cancer in women with vaginal bleeding was ten times higher than in asymptomatic patients (0.1 % vs 1.0%).Machtinger and coworkers (7) found that both age and symptomatology correlated with risk of malignancy.They reported that among post-menopausal women with bleeding, the risk of atypical hyperplasia or cancer was 10% compared with 0.9% in post-menopausal women without bleeding.A recent systematic review noted that the relative risk for atypical hyperplasia or cancer in post-menopausal compared with pre-menopausal women was 3.86 (95% CI, 2.92-5.11). (10)However, in this study, three cases (one malignant and two pre-malignant polyps) were found in reproductive-age women similar to that reported by Martinez et al, 2004. (26)The lower risk of malignancy in endometrial polyps in the younger women may be due to a possible spontaneous regression mechanism that is characteristic of the cycling endometrium in women of reproductive age.Age dependant association was reported by previous studies/ 9,27) Also, one case of atypical hyperplasia was recorded in an asymptomatic woman similar to reports of prior studies. (28,29)n this study, no significant association was found between sizes of polyps and the risk of malignancy.Similarly, Fernandez-Parra and co-workers (22) found no consistent association between size and pathology; the risk of cancer was 4.9% among post-menopausal women with a polyp size of 2-3 cm.but the risk decreased with increased polyp size although an association between the risk of malignancy and the size of polyps has been reported by other studies. (6,29)n this study the cancer was confined to the endometrial polyp in 24%, while the adjacent endometrium was affected in 76%.Most prior studies have reported overall rates of cancer.The possibility certainly exists that the cancers in these women arose independently of the endometrial polyp.Endometrial cancer in many women may simply arise in the endometrium and spread to an adjacent polyp.0} In this study no significant association was found between the risk of malignancy in endometrial polyps and other clinical risk factors such as obesity, hypertension, diabetes and the use of hormonal therapy or tamoxifen.This may be explained by inadequate sample size and inclusion of different age groups.Previous studies also reported inconsistent findings regarding this association.

Conclusion:
There is a small risk of malignancy in endometrial polyps.This risk is mainly in patients with advanced age, symptomatic vaginal bleeding and post-menopausal status.In these circumstances endometrial polyps should be managed aggressively as a case of potential cancer and removal for histology is mandatory.This study has limitations due to the small number of cases.Therefore, a larger prospective multicenter study is recommended.

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A peer reviewed jc wrnal QATAR MEDICAL JOURNAL They said about QMJ...

Table 1 :
Demographic and clinical characteristics of

Table 2 :
Histopathological types of endometrial polyps

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It was with great interest that I read the recent issue of the Qatar Medical Journal and my colleagues and I would extend our best wishes to you and your editorial board and, of course, our senior colleague, Dr Hajar A Hajar, Chairman of the Editorial Board.It is a splendid publication and from the quality of the scholarship quite obviously the QMJ is a peer reviewed journal of international standard".Your journal looks excellent.Of course most of it is general medical, beyond my area of expertise, but the presentation and layout are superb.It is a very nice at the beginning to have a historical article, and of course the figure that goes with this is beautiful.I know how much work it is running a journal such as this, and have to be congratulated".like to express my thanks and appreciation for sending me a copy of the new issue of Qatar Medical Journal, which I was happy to receive it.The style it was published is remarkable and I am sure that the readers would get benefit from the important features and contents of the journal".